Method of destroying tissue cells by electroporation

ABSTRACT

An apparatus and method for performing non-invasive treatment of the human face and body by electroporation in lieu of cosmetic surgery is provided. The apparatus comprises a high voltage pulse generator and an applicator having two or more electrodes in close mechanical and electrical contact with the patient&#39;s skin for applying the pulses to the patient&#39;s skin. The applicator may consist of two pieces with one electrode having a sharp tip and another having a flat surface. High voltage pulses delivered to the electrodes create at the tip of the sharp electrode an electric field high enough to cause death of relatively large subcutaneous fat cells by electroporation. Moving the electrode tip along the skin creates a line of necrotic subcutaneous fat cells, which later are metabolized by the body. Multiple applications of the electrode along predetermined lines on the face or neck create shrinkage of the skin and the subcutaneous fat volume underlying the treated area.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. application Ser. No. 13/556,455, filedJul. 24, 2012, now U.S. Pat. No. 8,647,338, which is a continuation ofU.S. application Ser. No. 12/1501,225, filed Jul. 10, 2009, now U.S.Patent No. 8,251,986, which is a continuation of U.S. application Ser.No. 11/106,835, now U.S. Pat. No. 7,938,824, filed Apr. 15, 2005, whichis a continuation of U.S. application Ser. No. 09/931,672, filed Aug.17, 2001, now U.S. Pat. No. 6,892,099, which claims priority to U.S.provisional application Ser. No. 60/267,106, filed Feb. 8, 2001 and toU.S. provisional application Ser. No. 60/225,775, filed Aug. 17, 2000,all of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to electroporation of tissuesand, specifically, to apparatus and methods for reducing subcutaneousfat deposits, performing virtual face lifts, and body sculpturing.

BACKGROUND OF THE INVENTION

“Cosmetic surgery” is a phrase used to describe broadly surgical changesmade to a human body with the usual, though not always, justification ofenhancing appearance. This area of medical practice constitutes anever-growing industry around the world. Obviously, where such aprocedure fails to deliver an enhanced appearance, the procedure failsto meet the desired goal. One of the reasons that the majority ofcurrent procedures fail to deliver upon their promise is that, for themost part, current procedures are invasive, requiring incisions andsuturing, and can have serious and unpleasant side effects, includingbut not limited to scarring, infection, and loss of sensation.

One of the more common forms of cosmetic surgery is the “face-lift.” Aface-lift is intended to enhance facial appearance by removing excessfacial skin and tightening the remaining skin, thus removing wrinkles. Aface-lift is traditionally performed by cutting and removing portions ofthe skin and underlying tissues on the face and neck. Two incisions aremade around the ears and the skin on the face and neck is separated fromthe subcutaneous tissues. The skin is stretched, excess tissue and skinare removed by cutting with a scissors or scalpel, and the skin ispulled back and sutured around the ears. The tissue tightening occursafter healing of the incisions because less skin covers the same area ofthe face and neck and also because of the scars formed on the injuredareas are contracting during the healing process.

Traditional face-lift procedures are not without potential drawbacks andside effects. One drawback of traditional cosmetic surgery is related tothe use of scalpel and scissors. The use of these devices sometimesleads to significant bleeding, nerve damage, possible infection and/orlack of blood supply to some areas on the skin after operation.Discoloration of the skin, alopecia (boldness), is another possible sideeffect of the standard cosmetic surgery. The overall quality of theresults of the surgery is also sometimes disappointing to the patientsbecause of possible over-corrections, leading to undesired changes inthe facial expression. Additionally, face-lift procedures require a longrecovery period before swelling and bruising subside.

The use of lasers to improve the appearance of the skin has been alsodeveloped. Traditional laser resurfacing involves application of laserradiation to the external layer of the skin--the epidermis. Destructionof the epidermis leads to rejuvenation of the epidermis layer. Thedrawback of the laser resurfacing procedure is possible discoloration ofthe skin (red face) that can be permanent.

Another laser procedure involves using optical fibers for irradiation ofthe subcutaneous tissues, such as disclosed in U.S. Pat. No. Re36,903.This procedure is invasive and requires multiple surgical incisions forintroduction of the optical fibers under the skin. The fibers deliverpulsed optical radiation that destroys the subcutaneous tissues as thetip of the fiber moves along predetermined lines on the face or neck.Debulking the subcutaneous fat and limited injury to the dermis alongthe multiple lines of the laser treatment results in contraction of theskin during the healing process, ultimately providing the face lift. Thedrawback of the method is its high price and possibility of infection.

Electrosurgical devices and methods utilizing high frequency electricalenergy to treat a patient's skin, including resurfacing procedures andremoval of pigmentation, scars, tattoos and hairs have been developedlately, such as disclosed in U.S. Pat. No. 6,264,652. The principledrawback of this technology is collateral damage to the surrounding andunderlying tissues, which can lead to forming scars and skindiscoloration.

Other forms of cosmetic surgery are also known. One example isliposuction, which is an invasive procedure that involves inserting asuction device under the skin and removing fat tissues. As with otherinvasive surgical procedures, there is always a risk of infection. Inaddition, because of the invasive nature of the procedure, physiciansusually try to minimize the number of times the procedure must beperformed and thus will remove as much fat tissue as possible duringeach procedure. Unfortunately, this procedure has resulted in patientdeaths when too much tissue was removed. Assuming successful removal ofexcess fat tissue, further invasive surgery may be required toaccomplish desired skin tightening.

The prior art to date, then, does not meet the desired goal ofperforming cosmetic surgery in a non-invasive manner while causingminimal or no scarring of the exterior surface of the skin and at thesame time resulting in the skin tightening.

Objects of the Invention

It is an object of the present invention to provide an apparatus andmethod which uses electroporation to cause necrosis of cells in thesubcutaneous layer of fat and the interior side of the dermis, resultingin the contraction and tightening of the skin. In particular, it is anobject of the present invention to provide method and apparatus forperforming face and neck lift and others similar procedures on the facein a non-invasive manner.

Another object of the present invention is to provide an apparatus andmethod for significant bulk reduction of the number of subcutaneous fatcells in the body, resulting in a significant weight loss.

Still another object of the present invention is to provide non-invasiveapparatus and method for cosmetic and weight loss procedures.

Still another object of the invention is to provide an apparatus andmethod for selective removal of fat in different areas to enablechanging the shape of the body, or body sculpturing.

SUMMARY OF THE DISCLOSURE

The present invention provides an apparatus and method for creation of acontrolled injury or alteration to the subcutaneous tissue and/orunderside of the dermis, with the following healing process leading tothe contraction of the skin; and/or to the controlled destruction of fatcells, leading to their permanent loss. In the present invention thedamage to the subcutaneous tissue, underside of the dermis, and/or fatcells is caused by electroporation.

An apparatus in accord with the current invention comprises a voltagepulse generator, an applicator with two or multiple electrodes ofdifferent shapes and sizes and a cable connecting the electrodes to thepulse generator. The pulse generator produces set of high voltage pulsesof predetermined amplitude, duration and number to cause necrosis in atreated area of subcutaneous tissues.

A method in accord with the current invention comprises application ofelectrical pulses to the electrodes positioned on the skin in atreatment area. For a face lift, flat and needle-like electrodes areused, the last one providing a strong and non-uniform electric fieldpredominantly normal to the surface of the skin. The amplitude, durationand number of applied pulses are selected to cause necrosis of fat cellsto a predetermined depth in the subcutaneous tissue and a limitednecrosis of the underside of the dermis. A number of lines ofpredetermined pattern are exposed to electroporation. Later, during thehealing process the skin on the treated area contracts. The injury tothe tissues made by electroporation is very gentle and selective; itdoes not produce scars on the epidermis, the most external layer of theskin.

A method of weight loss and body sculpturing in accord with the presentinvention comprises application of electroporation pulses to asignificant volume of fat tissue. In this case both electrodes are flatand attached to the arms of a forceps. The electrodes are moveabletowards and away from each other and are capable of pinching skin withunderlying subcutaneous fat and electroporating it. Application of flat,parallel electrodes produces a electric field is uniform in the tissuethat effects only fat cells.

For weight loss a voltage generator coupled to multiple needle typeelectrodes may be used.

In another embodiment of the present invention, an electroporationapparatus for bulk weight loss may comprise apparatus for production ofa pulsed magnetic field and its application to the area to be treated.In this embodiment of the present invention, a curl electric field forthe electroporation of subcutaneous fat is created by the pulsedmagnetic field. Curl electric field causes eddy currents in the tissueand at an appropriate amplitude above kills the fat cells.

BRIEF DESCRIPTION OF THE DRAWINGS

The objects and advantages of the present invention will be appreciatedfrom the following specification when read in conjunction with theaccompanying drawings wherein:

FIG. 1 is a schematic illustration of an apparatus with an applicatorhaving an array of symmetric electrodes shown during electroporationtreatment.

FIG. 2 is a schematic illustration of an apparatus with an applicatorhaving one flat electrode and one a needle like electrode shown duringelectroporation treatment.

FIG. 3 is a schematic illustration of different applicators of thepresent apparatus wherein FIG. 3 a illustrates an applicator with twoneedle like electrodes; FIG. 3 b illustrates an applicator having anarray of needle like electrodes; and FIG. 3 c illustrates applicatorhaving one flat electrode and one needle like electrode.

FIG. 4 a is a perspective view of a forceps type applicator with twoflat electrodes in an open position.

FIG. 4 b is a schematic illustration of the forceps flat electrodes inclosed position shown during electroporation treatment.

FIG. 5 is a schematic illustration of an apparatus for electroporationtreatment for weight loss with electrodeless applicator.

FIG. 6 is a frontal view of a human head with schematically shownelectroporation treatment for removal of the forehead wrinkles andglabellar frown lines.

FIG. 7 is a lateral view of a human head with schematically shownelectroporation treatment for a neck lift.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The term “electroporation” (EP) refers to the use of electric fieldpulses to induce microscopic pores in the cell membranes called“electropores”. Depending on the parameters of the electric pulse, anelectroporated cell can survive the pulse or die. The cause of death ofan electroporated cell is believed to be a chemical imbalance, resultingfrom the fluid communication with the extra cellular environment throughthe pores. The number and size of electropores created depends on theproduct of the amplitude E and duration t of the pulse. Below a certainlimit, no electropores are induced at all. This limit is different fordifferent cells and depends, principally, on their sizes. The smallerthe cell, the higher the product of the amplitude and duration must beto induce pores. Above the lower limit the number of pores and theireffective diameter increases with the product Et. Until an upper limitis achieved, cells survive pulsing and restore their viabilitythereafter. Above the upper limit the pores diameters and number becometoo large for a cell to survive. It cannot repair itself by anyspontaneous or biological process and dies. As noted, a cell'svulnerability to an electric field depends on its size: the larger thecell, the lower the electric field required for killing it. If cells ofdifferent sizes are exposed to the same electric field, the largestcells are the first to die. Thus, application of an electric fieldhaving preselected parameters can result in selectively killingparticular cells.

A desirable target for cell death using the present invention is adiposetissue, commonly called fat. Adipose cells do not proliferate in adults.Their number is fixed at a very early age. Adipose cells can changetheir size by accumulating or loosing lipids and be responsible forsignificant, up to two-fold increase in the body weight. Cutting down inthe number of large adipose cells results in a significant weight lossin the fat tissue and the whole body. If fat cells are destroyed by anymeans, their content is metabolized by the body, i.e., scavenged bymacrophages, and their number is not restored. The loss of adiposecells, then, is permanent.

Adipose tissue consists of lipid-filled cells ranging in size from 25 to200 microns. An applied electric field affects the various sized cellsdifferently as previously mentioned. For example, if an electric field,equal to the upper electroporation limit for 100 micron cells (about10-20 V/mm) is applied to a fat tissue, all cells with sizes from 100micron and above, will die. The dead cells will be disposed later bymacrophages, and the body will metabolize the lipids stored in thesecells. Small adipose cells, for which the applied electric field isbelow the upper electroporation limit, survive any number of electricpulses without any morphological or functional damage.

Pulsed electric fields can be applied to fat deposits inside the body bydifferent methods. In a first method two electrodes are applied to theskin over the fat tissue at some distance from each other and electricmicrosecond pulses are applied by the electrodes to the tissue. Thepulse electric field, created by these two electrodes is non-uniform; itis higher near the electrodes and decreases with the depth. The electricfield at the fat deposits should reach several tens of volts per mm tobe able to kill adipose cells of large diameters. At the skin level thenon-uniform electric field will be significantly higher. To be harmlessfor the skin cells, the field should not exceed the value of the upperelectroporation limit for skin cells. The cells in the epidermic basallayer of the skin, which is responsible for the mitotic division andcontinuous rejuvenation of the skin, have dimensions of about 10 micronsor less (6-10 microns). This is 10 or more times less than that of thetargeted adipose cells, which is about 100 microns and larger as notedearlier. The upper electroporation limit for the skin cells inaccordance with their size is therefore about 10 times higher than thatof adipose cells of 100 microns diameter.

A second method of applying an electric field to the subcutaneousadipose tissue or the skin is by applying short magnetic pulsespreferentially normally to the skin. The transient magnetic fieldcreates curl electric field in the skin and the underlying tissues. Thiscurl electric field causes eddy currents in the cells. If the magnitudeof this transient electric field reaches the upper electroporation limitfor the cells, it will kill them exactly as does the potential electricfield created by charged electrodes.

The depth of penetration of the electric field in the skin and the fattissue under it depends on the distance between the electrodes, theirshape and size. The larger the size of electrodes and the distancebetween them, the deeper the penetration will be. If the electrodes aresmall enough and the distance between them is short, the electric fieldpenetrates only into the skin and does not reach the underlying tissues.

If pulsed electric field penetrates only in the skin and its amplitudeis high enough to kill skin cells (several hundred volts per mm),electroporation can be used for selective cell killing. The dead cellsare removed by macrophages and the skin shrinks during the healingprocess. This skin shrinkage can be planned in advance both in terms ofdirections and degree. By selecting a number, direction and length ofthe electroporation “cuts” the operator can control the future shrinks.This method can be used for correcting wrinkles and skin pouches on theface, the neck, and on the upper and lower eye lids.

The skin electroporation treatment together with fat reducingelectroporation treatment can be used as alternative to cosmetic surgeryfor the face lift, the upper and lower eye lid surgery, the foreheadlift and body sculpturing practically in all parts of the human body.

An electroporation treatment presents several notable advantages overpresent cosmetic surgery procedures. First, an electroporation treatmentis sterile. The most upper layer of the skin, comprising horny deadcells, is very resistant to any damage from an electroporationtreatment; it protects the lower layers of the skin from infection.

The electroporation virtual facelift and body sculpturing can beperformed in step by step fashion in a multi-session process. Thismethod allows taking into account actual results of previous sessionsand directs process of reshaping of the face or body to desiredobjectives. The treatment can be performed by a medical professional orby the patient him/herself.

With the foregoing generalized explanation of the present invention,apparatus in accord therewith may be described. Referring to FIG. 1, anelectroporation system 10 in accord with the invention is schematicallyshown with a cross section of a piece of skin 12 with subcutaneoustissue 14 during electroporation treatment. Electroporation system 10includes a power supply 16 for generating high voltage pulses that aresent though an appropriate electrical connector 18 to an applicator 20.Applicator 20 includes electrodes 22 and 24 that engage skin 12 and willbe appropriately insulated to ensure safe handling. Additionally, theapplicator will preferably be configured so as to ensure ease ofhandling, and thus could take many forms. The electrodes 22 and 24 maytake the form of needle electrodes. The electric field created betweenthe electrodes 22 and 24 is depicted with field lines 26 and is appliedto the skin 12 and subcutaneous tissue or fat 14. In the areas close tothe electrodes the electric field has an amplitude exceeding the upperelectroporation limit, thus causing death to fat cells. This area of fatcell necrosis is indicated at 28,

In FIG. 2 an alternative embodiment 40 of the present invention is shownwith an applicator having two members: a needle-like electrode 42 and aflat electrode 44. If desired, the system 40 may include an insulatinghandle 46 configured to be held by an operator to facilitate the manualmanipulation of the electrode 42. The high voltage pulse power supply 16is connected to the applicator electrodes 42 and 44 by appropriateelectrical connectors 48. Both electrodes 42 and 44 are engaged withskin 12. Electric field lines 26 depict an electric field between theelectrodes 42 and 44. The area 28, where the electric field is thehighest, is the treatment area where the amplitude of the electric fieldexceeds the upper electroporation limit and causes cell death.

In FIG. 3 different versions of applicators are schematically shown.FIG. 3 a illustrates an applicator 60 with two needle-like electrodes64. FIG. 3 b shows an applicator 64 with an array of needle-likeelectrodes 64. FIG. 3 c depicts an applicator 66 like that shown in FIG.2 and comprising a needle-like electrode 42 and a flat electrode such aselectrode 44.

FIGS. 4 a and 4 b illustrate another embodiment 80 of an electroporationsystem in accord with the present invention useful for bulk fatreduction. System 80 includes an applicator 82 comprising a body orsupport member 84 supporting calipers or forceps apparatus 86. Thecalipers apparatus 86 includes a pair of pivotable arms 88 mounted atthe distal end thereof. The arms 88 support a pair of electrodes 90 and92. Applicator 82 may include a pistol grip 94 mounted on a proximal endof the elongated tubular support member 84 for enabling ease ofmanipulation of same. The electrodes 90 and 92 are mounted on a moveablelinkage so that the electrodes are moveable toward and away from eachother. A power supply 16 and electrical connectors 48 are also includedwithin a system 80 to provide pulse electrical power to the electrodes90 and 92.

FIG. 4 b schematically illustrates an electroporation treatmentutilizing system 80. As shown in the figure, a “fold” of skin 12 withunderlying subcutaneous tissue—fat—14 is compressed between arms 88 andthus electrodes 90 and 92. A uniform electric field 26 is applied to theskin 12 and subcutaneous tissue 14 clamped between electrodes. Only thelarge fat cells are killed in this field configuration because the cellsof the dermis are spared death because of their small size.

FIG. 5 schematically illustrates another embodiment of the presentinvention including an electrodeless system 100. System 100 includes ahigh pulse current power supply 16 and an appropriate electricalconnector 18 extending to an applicator 102. Applicator 102 comprises ahousing 104 and an electromagnetic coil 106 disposed therein. Coil 106generates a magnetic field 108 that is applied to the skin 12 and thesubcutaneous tissues 14. The pulsed magnetic field 108 in the tissueexists only about 10 microseconds. The energy of rapidly changingmagnetic field transforms into a curl electric field 110, which createseddy currents in tissue and provides the electroporation treatment forkilling the fat cells in the tissue 14. Preferably, the curl electricfield generated in the subcutaneous tissue is in the range of 30 to 50Volt/mm, and the duration of the pulses is 5 to 20 microseconds.

FIG. 6 schematically illustrates a frontal view of human head 120 withglabellar frown lines 122 and forehead wrinkles 124. An embodiment ofthe present invention Such as system 40 is shown in application.Electrode 44 is shown applied to the forehead and the needle electrode42 is moved over the skin where treatment is desired. Moving theelectrode tip along the skin creates a line of necrotic subcutaneous fatcells, which later are metabolized by the body. An exemplary line oftreatment 126 is shown in the Figure. Multiple applications of theelectrode along predetermined lines on the face or neck create shrinkageof the skin and the subcutaneous fat volume underlying the treated area.

FIG. 7 depicts a lateral view of a human head 130 during a neck liftelectroporation procedure using an electroporation system in accord withthe present invention such as system 40. The figure illustrates anexemplary line of electroporation treatment 132.

The present invention having thus been described, other modifications,alterations, or substitutions may now suggest themselves to thoseskilled in the art, all of which are within the spirit and scope of thepresent invention. It is therefore intended that the present inventionbe limited only by the scope of the attached claims below.

What is claimed is:
 1. A system for sculpting a human body comprising:an applicator comprising first and second electrodes defining atreatment area therebetween, the treatment area adapted to accept aportion of the human body comprising at least one of skin, subcutaneoustissue, and fat; and a generator operably connected to the applicatorand adapted to apply a plurality of electrical pulses between the firstand second electrodes in an amount sufficient to irreversibly open poresin fat cells of the portion of the human body.
 2. The system of claim 1,wherein the applicator is adapted to retain the portion of the humanbody within the treatment area during the application of electricalpulses.
 3. The system of claim 1, wherein the first and secondelectrodes are positioned on opposing sides of the treatment area. 4.The system of claim 1, wherein the generator is further adapted to applyelectrical pulses whose amplitude is in a range of 20 Volt/mm and 2000Volt/mm.
 5. The system according to claim 1, wherein the generator isfurther adapted to apply electrical pulses whose amplitude is above 20Volt/mm.
 6. The system of claim 1, wherein the generator is furtheradapted to apply electrical pulses whose duration is in a range of 10microseconds and 100 milliseconds.
 7. The system of claim 1, wherein thegenerator is further adapted to apply electrical pulses whose amplitudeis in a range of 20 Volt/mm and 2000 Volt/mm and whose duration is in arange of 10 microseconds and 100 milliseconds.
 8. The system of claim 1,wherein the applicator comprises a grip and first and second opposedarms configured to move toward each other to forcibly retain the portionof the human body by compression.
 9. The system of claim 1, wherein theportion of the human body is a skin fold.
 10. A method for sculpting ahuman body comprising: providing: an applicator comprising first andsecond electrodes defining a treatment area therebetween, the treatmentarea adapted to accept a portion of the human body comprising at leastone of skin, subcutaneous tissue, and fat, and a generator operablyconnected to the applicator; engaging the applicator with a surface ofskin on the human body; retaining the portion of the human body withinthe treatment area; and applying a plurality of electrical pulsesbetween the first and second electrodes in an amount sufficient toirreversibly open pores in fat cells in the retained portion of thehuman body.
 11. The method of claim 10, wherein the portion of the humanbody comprises all of skin, subcutaneous tissue and fat.
 12. The methodof claim 10, wherein the first and second electrodes are positioned onopposing sides of the treatment area.
 13. Repeating the method of claim10 on a plurality of different portions of the human body according to apre-determined treatment plan.
 14. The method of claim 10, wherein thestep of applying further comprises applying electrical pulses whoseamplitude is in a range of 20 Volt/mm and 2000 Volt/mm.
 15. The methodaccording to claim 10, wherein the step of applying a plurality ofelectrical pulses further comprises applying electrical pulses whoseamplitude is above 20 Volt/mm.
 16. The method of claim 10, wherein thestep of applying a plurality of electrical pulses further comprisesapplying electrical pulses whose duration is in a range of 10microseconds and 100 milliseconds.
 17. The method of claim 10, whereinthe step of applying a plurality of electrical pulses further comprisesapplying electrical pulses whose amplitude is in a range of 20 Volt/mmand 2000 Volt/mm and whose duration is in a range of 10 microseconds and100 milliseconds.
 18. The method of claim 10, wherein the applicatorfurther comprises a grip and first and second opposed arms configured tomove toward each other, and wherein the step of retaining furthercomprises forcibly retaining the portion of the human body bycompression via the first and second opposed arms.
 19. A method for askin tightening and fat reduction treatment comprising: providing: anapplicator comprising first and second electrodes defining a treatmentarea therebetween, the treatment area adapted to accept a portion of thehuman body comprising at least one of skin, subcutaneous tissue, andfat, and a generator operably connected to the applicator; engaging theapplicator with a surface of skin on the human body; retaining theportion of the human body within the treatment area; applying a firstplurality of electrical pulses between the first and second electrodesin an amount sufficient to irreversibly open pores in fat cells of theportion of the human body; and applying a second plurality of electricalpulses between the first and second electrodes in an amount sufficientto irreversibly open pores in skin cells of the portion of the humanbody.
 20. Repeating the method of claim 19 on a plurality of differentportions of the human body according to a pre-determined treatment plan.